Dr Craig Donaldson, University of the West of England

Stem cell transplantation (SCT) is sometimes required in the treatment of childhood leukaemia to enable the child’s damaged bone marrow to resume production of normal blood cells. It is a delicate and risky process and is only used in certain groups of children, such as those who repeatedly relapse.

The Bone Marrow Transplant Unit at the United Bristol Healthcare Trust has an excellent track record for developing new methods of improving the results of SCT in patients with leukaemia. Much of this work is aimed at improving the cure rate of SCT without subjecting patients to the life-threatening complication of graft versus host disease (GVHD).

Treatment with a drug called Campath which suppresses the immune system has been crucial to this work. It is known, however, that Campath not only suppresses GVHD but also suppresses an important beneficial side-effect of SCT known as graft versus leukaemia (GVL) in which stem cells transplanted from a donor help to kill the leukaemia cells remaining in the patient’s bone marrow. Suppression of GVL causes a significant proportion of patients to relapse after their transplants and eventually to die of leukaemia.

Dr Donaldson and colleagues are studying a type of white blood cell called the Natural Killer T-cell (NKT-cell) which they believe plays a key role in GVL. They are studying the development of donor NKT-cells in the patient’s bone marrow after SCT in order to identify ways of exploiting the effects of this important cell.

This two-year grant is an extension of a previous two years’ funding during which time the team has already made good progress in understanding the function of the NKT-cell.

During the period of the current grant, the team are studying the recovery of NKT cells in patients following SCT and investigating what factors – such as the use of Campath, and the intensity of pre-transplant conditioning - affect this recovery.

In the longer term, the team want to investigate whether the recovery of NKT-cells influences the probability of GVHD and/or leukaemic relapse. If these studies suggest that NKT-cells are important for the cure of leukaemia post-transplant, the team will seek to develop immunotherapy protocols to stimulate the production and activity of these unique cells.

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